General classification of factors
For a systematic understanding of pharmacotherapy, all conditions capable of altering the effect of a medicinal product (MP) are divided into four logical groups:
- Properties of the substance itself — chemical structure, physicochemical parameters, and quantitative characteristics (doses, concentrations).
- Pharmaceutical factors — the chosen dosage form and its manufacturing technology.
- Patient-related factors — current functional state, pathologies, sex, age, body weight, and genetics.
- Environmental and regimen factors — conditions of use (repeated administration, combinations), time of day, and environmental parameters.
Role of the molecule and dosage form
The fundamental profile of a drug is determined by its chemical structure. Substances of the same chemical group (e.g., benzodiazepines) produce a similar spectrum of effects. For a molecule to bind to a receptor, it must have specific functional groups, the correct spatial orientation, and an appropriate size.
The dosage form itself does not change the mechanism of action, but it critically affects pharmacokinetics. The site and rate of absorption depend on the form, and therefore the time of onset of the effect and its duration. Modern technologies make it possible to create prolonged-release forms, as well as use excipients to improve taste or reduce irritating effects.
Patient: sex, age, and body weight
Individual parameters of the body require careful dose adjustment:
- Sex. Male sex hormones stimulate liver enzymes, so the metabolism of a number of drugs (paracetamol, verapamil, benzodiazepines, ethanol) is accelerated in men. Women have a higher risk of specific arrhythmias (torsades de pointes) when taking antiarrhythmic agents, and morphine can cause paradoxical excitation.
- Age. The two most vulnerable groups are newborns and the elderly. In neonates, liver enzymes are poorly developed, renal function is reduced, and the blood-brain barrier (BBB) is highly permeable, leading to increased toxicity (e.g., of chloramphenicol). In elderly individuals (over 60 years of age), absorption processes slow down, albumin levels decrease, and blood flow drops. Potent drugs are prescribed to them at 2/3 of the standard dose.
- Body weight. The concentration of the substance is inversely proportional to weight. In cachexia (emaciation) or dehydration, the dose must be reduced by 1.5–2 times to avoid overdose.
Influence of diseases and genetics
The effect of a drug directly depends on the baseline background. For instance, acetylsalicylic acid reduces only elevated temperature, while cardiac glycosides exhibit a cardiotonic effect specifically in heart failure. Local pathologies are also important: the efficacy of local anesthetics drops in the focus of inflammation, and that of sulfonamides in a purulent wound.
Systemic diseases (especially of the kidneys and liver) lead to cumulation (accumulation) of the substance. For example, in renal failure, the half-life of ampicillin increases from 1.3 to 20 hours.
Genetic factors are studied by pharmacogenetics. Gene mutations lead to enzymopathies — disruptions in the structure or function of enzymes. This slows down drug metabolism and causes toxic reactions. The most striking example is idiosyncrasy (atypical reaction). In case of a glucose-6-phosphate dehydrogenase enzyme defect, taking antimalarial drugs provokes massive hemolysis of erythrocytes.
Briefly: answers to topical questions
What types of body reactions occur with repeated administration of medications?
Upon repeated administration of medications, the pharmacological effect can quantitatively increase or decrease, as well as qualitatively change with the appearance of new reactions. The following main phenomena occur:
- Cumulation (Cumulatio) — accumulation of the substance itself or the effects it causes in the body.
- Sensitization — development of hypersensitivity to the drug substance; drug allergy may develop upon repeated administration.
- Tolerance (habituation) — a decrease in sensitivity to the therapeutic and toxic effects of the drug, developing within a period ranging from a few days to months.
- Drug dependence — an urgent need for continuous or periodic intake of the substance to achieve euphoria or relieve withdrawal syndrome.
How do circadian rhythms and time of day alter drug pharmacodynamics?
Circadian rhythms and time of day cause rhythmic changes in the body's sensitivity to drugs and fluctuations in the final pharmacological effect. These changes are described by the following concepts:
- Chronesthesia — daily changes in sensitivity to a substance associated with fluctuations in the number and sensitivity of receptors, enzyme activity, and membrane permeability.
- Chronergy — an integral indicator of the final effect, determining fluctuations in the potency and duration of drug action depending on the time of administration.
To account for these daily rhythms of sensitivity, reactivity, and pharmacokinetics, a chronotherapeutic approach using dynamic doses instead of static regimens is applied.
How exactly do liver diseases alter the metabolism and bioavailability of drugs?
Liver diseases slow down the biotransformation of drug substances due to a decrease in liver enzyme activity and a reduction in hepatic blood flow. This leads to the following changes:
- The rate of drug metabolism decreases, causing a prolongation of their action.
- Cumulation (accumulation) of the substance in the body occurs, increasing the risk of toxic effects.
- The synthesis of biologically active forms of certain substances, such as vitamin D metabolites, decreases.
To memorize the 4 groups of factors, use the mnemonic "SPPS": Substance (chemistry, dose), Pharmaceutical (form), Patient (age, diseases, genetics), Environment (regimen, ecology).
Class and exam questions
Does the dosage form change the nature of the drug's action?
No, the dosage form does not change the nature of action (mechanism), but it strictly determines pharmacokinetics: the site and rate of absorption, the rate of onset, and the duration of the effect.
Why is it necessary to change the dosage in kidney diseases?
A decrease in the excretory function of the kidneys causes drugs (especially those excreted unchanged) to leave the body more slowly. This causes their cumulation and sharply increases the risk of toxic effects.
What is idiosyncrasy in pharmacology?
This is a genetically determined, atypical (perverted) reaction to a substance. It arises due to a deficiency of certain enzymes, for example, erythrocyte hemolysis when taking quinine in people with G6PD deficiency.
What else to study on this topic
- Perinatal pharmacology: placental barrier permeability and effects on the fetus.
- Pharmacokinetic changes in geriatrics: why albumin binding drops.
- Influence of local pathologies (inflammation, pus) on the efficacy of topical agents.
- Gender differences in receptor sensitivity to opioid analgesics.
- Enzymopathies: mechanisms of genetically determined slowing of drug metabolism.
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